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Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2

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Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2. / Verkest, Clement; Schaefer, Irina; Nees, Timo A; Wang, Na; Jegelka, Juri M; Taberner, Francisco J; Lechner, Stefan G.

In: NAT COMMUN, Vol. 13, No. 1, 1365, 15.03.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Verkest, C, Schaefer, I, Nees, TA, Wang, N, Jegelka, JM, Taberner, FJ & Lechner, SG 2022, 'Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2', NAT COMMUN, vol. 13, no. 1, 1365. https://doi.org/10.1038/s41467-022-28974-6

APA

Verkest, C., Schaefer, I., Nees, T. A., Wang, N., Jegelka, J. M., Taberner, F. J., & Lechner, S. G. (2022). Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2. NAT COMMUN, 13(1), [1365]. https://doi.org/10.1038/s41467-022-28974-6

Vancouver

Verkest C, Schaefer I, Nees TA, Wang N, Jegelka JM, Taberner FJ et al. Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2. NAT COMMUN. 2022 Mar 15;13(1). 1365. https://doi.org/10.1038/s41467-022-28974-6

Bibtex

@article{3ced7689f6ed4494bdc3ce2a83543906,
title = "Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2",
abstract = "A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.",
keywords = "Cytoskeleton/metabolism, Ion Channels/metabolism, Mechanotransduction, Cellular/physiology",
author = "Clement Verkest and Irina Schaefer and Nees, {Timo A} and Na Wang and Jegelka, {Juri M} and Taberner, {Francisco J} and Lechner, {Stefan G}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = mar,
day = "15",
doi = "10.1038/s41467-022-28974-6",
language = "English",
volume = "13",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2

AU - Verkest, Clement

AU - Schaefer, Irina

AU - Nees, Timo A

AU - Wang, Na

AU - Jegelka, Juri M

AU - Taberner, Francisco J

AU - Lechner, Stefan G

N1 - © 2022. The Author(s).

PY - 2022/3/15

Y1 - 2022/3/15

N2 - A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.

AB - A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.

KW - Cytoskeleton/metabolism

KW - Ion Channels/metabolism

KW - Mechanotransduction, Cellular/physiology

U2 - 10.1038/s41467-022-28974-6

DO - 10.1038/s41467-022-28974-6

M3 - SCORING: Journal article

C2 - 35292651

VL - 13

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 1365

ER -